Therapeutic methods involving the co-administration of drugs may be used in cases where larger doses of a single agent would not have a therapeutic benefit or would result in unacceptable toxicity or side effects, or where multiple mechanisms of action may be beneficial. This approach is commonly used in the treatment of pain, viral or bacterial infection, asthma, hypertension and cancer. For example, opioid analgesics may be combined with other analgesics such as acetaminophen or non-steroidal anti-inflammatory drugs (NSAIDs, see generally, U.S. Pat. No. 6,451,806). Similarly, in the field of migraine therapeutics, it has been reported that the co-administration of triptans together with NSAIDs results in better overall relief than the administration of either agent alone (U.S. Pat. No. 6,586,458).
Unfortunately, there are instances in which one drug in a combination, due to an unwanted pharmacological effect on the gastrointestinal tract, impairs the absorption of other drugs from a patient's gastrointestinal tract. This appears to be true both for drug combinations involving the use of opioids (Crighton, et al., Anesth. Analg. 87:445-449 (1998)), and for those involving the use of triptans (Seaber, et al., Eur. J. Clin. Pharm. 53:229-234 (1997)). Impaired absorption of one component in such combinations can lead to a delayed onset of action for this component and to a less than optimal overall therapeutic effect.
A number of approaches have been taken in an attempt to compensate for poor absorption of drugs from the gastrointestinal tract of patients. These have included the co-administration of an agent that enhances absorption (U.S. Pat. No. 5,968,972) or that increases gastric motility (U.S. Pat. No. 6,479,551). Alternatively, drugs can be administered by a route that avoids a patient's gastrointestinal tract, e.g., using transmucosal or transdermal delivery (U.S. Pat. No. 5,624,677; U.S. Pat. No. 6,143,278). While these methods may be useful for certain therapies, alternative approaches would be desirable.